NONSPECIFIC-BINDING OF ADVANCED-GLYCOSYLATION END-PRODUCTS TO MACROPHAGES OUTWEIGHS SPECIFIC RECEPTOR-MEDIATED INTERACTIONS

On binding to murine peritoneal macrophages, maleylated BSA exhibited saturable-binding kinetics, with about 24000 sites/cell. Prolonged inc ubation of BSA with > 20 mM glucose or 2 months incubation with greate r than or equal to 0.5 M glucose induced the modified protein to readi ly bind non-specifically to both cell and tube surfaces. Kinetic studi es on the binding of advanced glycated end-products (AGEs) and other m odified proteins to macrophages and hepatocytes showed no evidence for specific receptor binding, as neither binding saturation nor cross-co mpetition (homologous or heterologous) was detected. Although there wa s evidence for uptake of BSA which had been incubated with 0.5 M gluco se for 2 months, there was no uptake or degradation of AGEs which had been produced at physiological concentrations of glucose. This has imp lications for the role of macrophages in the recognition of AGEs, and suggests that the non-specific binding may be important in adhesion of AGEs, particularly in poorly controlled diabetics, and might act as a 'damage limitation' mechanism in the potential development of diabeti c complications, while low macrophage levels in the blood could seriou sly potentiate the long-term effects of non-enzymic post-translational protein modifications.